Mass spectrometry (MS) is an analytical technique utilized to produce spectra of the mass-to-charge ratios (or m/z values, or more simply “masses”) of ions produced from molecules of a sample of interest. The obtained spectra of masses are utilized to identify the molecules in the sample by correlating the measured masses with the known masses of ions associated with specific molecules. In a typical MS instrument, a sample is ionized and the produced ions are subsequently separated in a mass analyzer according to their mass-to-charge ratio. The ions are detected by an ion detector, and the signal derived from the output of the ion detector is displayed as a spectrum of the relative abundance of ions as a function of their mass-to-charge ratios.
Tandem mass spectrometry (MS-MS) utilizes multiple stages of mass spectrometry, which are usually separated by some form of ion fragmentation device such as a collision cell. MS-MS is particularly useful when the sample to be analyzed is a complex mixture of many distinct molecular species. MS-MS can be utilized to produce structural information about a compound by fragmenting specific ions inside the mass spectrometer and identifying the resulting fragment ions. This information can then be pieced together to generate structural information about the intact molecule. A typical tandem mass spectrometer has two mass analyzers separated by a collision cell into which an inert gas (e.g., argon, nitrogen) is admitted to collide with the selected sample of ions, causing the desired fragmentation. The first mass analyzer stage is used to select an ion mass or range of ion masses (“precursor” or “parent” ions) to transmit to the collision cell for fragmentation. The collision cell produced fragment ions (“product” or “daughter” ions) from the precursor ions, and transmits the fragment ions to the second mass analyzer stage. The second mass analyzer stage then sorts the fragment ions by mass and transmits them to the ion detector. Typically, the first mass analyzer stage transmits only a limited number of molecular species so that after fragmentation the resulting mass spectrum of product ions is simple enough that the mass peaks of the fragment ions can be identified with the correct precursor ion.
The mass analyzer(s) utilized in an MS or MS-MS instrument is often configured as a linear quadrupole ion guide. A linear quadrupole ion guide consists of a set of four parallel rod-shaped electrodes positioned at a radial distance from a central axis (i.e., the main optical axis of ion transmission), and spaced around the central axis so as to surround an axially elongated ion guide volume leading from an ion entrance end to an axially opposite ion exit end. To implement mass analysis or mass filtering, both radio frequency (RF) potentials and direct current (DC) potentials are applied to the ion guide electrodes so as to generate a composite RF/DC electric field effective for limiting the motions of ions of selected masses in directions radial to the central axis. Under the constraints imposed by this ion confining field, ions transmitted through the entrance end travel through the ion guide volume in complex trajectories around the central axis and generally in the resultant direction of the exit end. However, the operating parameters of the RF/DC field are set so as to impose mass-dependent stability limits on the motions of ions in the ion guide volume. The result is that only ions of selected masses (typically a single mass or narrow mass range) are able to travel through the entire axial length of the ion guide in stable trajectories focused along the central axis, and thereby pass through the exit end. On the other hand, ions of other (non-selected) masses have unstable trajectories. The amplitude of the radial oscillations of unstable ions grows as they travel through the quadrupole until they are no longer able to be contained by the ion confining field. Consequently, these non-selected, unstable ions are removed from the ion guide volume and do not reach the exit end of the ion guide.
The strength of the electric fields is ideally net zero on the central axis of the quadrupole ion guide. Thus, quadrupole transmission is well defined for ions that enter or exit the quadrupole field very close to the central axis, or that have a very narrow range of transverse offset relative to the instantaneous RF phase at the time the ions enter or exit the quadrupole field. However, it has been known for many years that ion transmission efficiency into and out of a quadrupole is generally poor. The fringe fields at the axial ends of the finite-length quadrupole will cause the ion orbits to be unstable as they pass through the fringe field (field termination) area, especially when the parameters are tuned to pass a very narrow range of masses as in the case of a typical mass filter. The defocusing forces experienced by ions in the fringe field can be much stronger than the focusing forces provided in the quadrupole guide volume. Ions approaching the quadrupole field at too far of a distance away from the central axis, or with too much of a transverse velocity component, can be lost before having a chance to become stabilized in the quadrupole field. Ions may also be lost in a transverse direction by encountering a strong RF amplitude at a given instant of time. The more time an ion spends in the fringe field, the more likely the ion will follow an unstable path and be removed from the ion beam. Thus slower ions, i.e., higher-mass ions and ions in beams of lower average kinetic energy, tend to be more adversely affected by the fringe field than faster ions. On the other hand, transmitting ions at low kinetic energy into the quadrupole may be desirable for increasing mass resolution.
Two well-known devices have been used to alleviate the instabilities described above. One device is known as a Brubaker pre-filter or post-filter (depending on its position relative to the main quadrupole rods), which is a short section of quadrupole rods at the end of the main mass filter quadrupole with the DC field removed but carrying (most of) the RF field of the main rods. While the Brubaker lens works in a satisfactory manner in many systems, it adds some length to the overall assembly that in some cases may be undesirable. A second device is known as a Turner-Kruger lens, which has one or more cylindrical or conical lenses that extend a small length inside the quadrupole rods. This approach also is satisfactory in some systems but may have a limited transmission efficiency of ions into (or out from) the quadrupole field. In both cases, the intent is to keep the ions both close to the center of the quadrupole field while transitioning into (or out from) the quadrupole field as well as ensuring that the ion orbit remains stable in that transition zone. These devices have been used for many years and are relatively well understood.
However, it would be desirable to further improve the transmission of ions into or out from a mass filter or other linear quadrupole ion guide, and/or to shorten the length of the transition while maintaining high transmission.